Combination therapy with sulfonylureas and metformin and the prevention of death in type 2 diabetes: a nested case-control study

Authors

  • Laurent Azoulay PhD,

    1. Division of Clinical Epidemiology, SMBD-Jewish General Hospital, Montreal, Quebec, Canada
    2. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
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  • Verena Schneider-Lindner MD, MSc,

    1. Division of Clinical Epidemiology, SMBD-Jewish General Hospital, Montreal, Quebec, Canada
    2. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
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  • Sophie Dell'Aniello MSc,

    1. Division of Clinical Epidemiology, SMBD-Jewish General Hospital, Montreal, Quebec, Canada
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  • Alicia Schiffrin MD,

    1. Division of Endocrinology, SMBD-Jewish General Hospital, Montreal, Quebec, Canada
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  • Samy Suissa PhD

    Corresponding author
    1. Division of Clinical Epidemiology, SMBD-Jewish General Hospital, Montreal, Quebec, Canada
    2. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
    • Division of Clinical Epidemiology, SMBD-Jewish General Hospital, 3755 chemin de la Côte-Sainte-Catherine, Montreal, Quebec H3T 1E2, Canada.
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  • SS has participated in advisory board meetings, conferences and participated as a speaker in scientific meetings by various companies (AstraZeneca, Boehringer Ingelheim, Glaxo SmithKline, Sanofi Aventis, Merck, Pfizer and Sepracor) and SS has received research grants from AstraZeneca, Wyeth, Glaxo Smith Kline and Organon. All other authors have no conflicts of interest to declare.

Abstract

Purpose

To determine whether combination of sulfonylureas and metformin increases the risk of death from any cause in patients with type 2 diabetes.

Methods

A nested case-control study was conducted within a population-based cohort from the UK General Practice Research Database (GPRD). The cohort included patients over the age of 40 who were prescribed a first oral hypoglycaemic agent between 1 January 1988 and 30 June 2008. Cases included all patients who deceased during follow-up. Up to 10 controls were matched to each case on year of birth, date of cohort entry (±1 year) and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RRs) of death from any cause associated with the use of combination of sulfonylureas and metformin, relative to sulfonylurea monotherapy.

Results

The cohort comprised 84 231 users of oral hypoglycaemic agents, of whom 14 996 died from any cause during a mean of 4.3 years of follow-up (mortality rate 4.1 per 100 per year). Patients currently exposed to a combination of sulfonylureas and metformin were at a decreased risk of death from any cause compared to patients exposed to sulfonylurea monotherapy (adjusted RR: 0.77, 95%CI: 0.70, 0.85). Similar results were obtained for patients currently exposed to metformin monotherapy (adjusted RR: 0.70, 95%CI: 0.64, 0.75) when compared to sulfonylurea monotherapy. Patients had to be exposed to the combination therapy for at least 4 months prior to index date to experience a lower risk of mortality compared to sulfonylurea monotherapy.

Conclusions

The combination of sulfonylureas and metformin does not increase the risk of death. In contrast, it may moderately reduce this risk compared to sulfonylurea monotherapy. Copyright © 2010 John Wiley & Sons, Ltd.

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